Biochemistry effects of tumor

and tumor Markers

Dr. Sharifah Sakinah Syed Alwi

Objectives

 To briefly introduce cancers, their incidence,

some common terms, and staging system.
 To be familiar with the definition of tumor
markers, and characteristics of an ideal tumor
marker.
 To know various applications of tumor marker
detection
Lecture outlines

 Overview
 Types of tumor markers
 Applications of tumor marker detection:
 Screening
 Prognosis
 Monitoring effectiveness of therapy and
disease recurrence
Overview

 Cancer is the second leading cause of death in

North America, accounting for > 500,000 deaths
annually.

 It is estimated that 45% of males and 38% of

females will develop invasive cancer in their
lifetime.
 Overview, continued…

 Cancer refers to the uncontrolled growth of cells that can

develop into a solid mass or tumor & spread to other
areas of the body.
 The formation (tumorigenesis) & spreading (metastasis)
of tumors are caused by a complex combination of
inherited and acquired genetic mutations
 During tumorigenesis, these mutations include activation
of growth factors e.g.
 Epidermal Growth Factor (EGF) & oncogenes (e.g. K-ras), in
combination with inhibition of apoptosis, tumor suppressor, and
cell cycle regulation genes.
Overview, continued…

 Cancer severity is generally classified by a combination of several

factors.

 Depending on the type of cancer, these factors include:

 Tumor size
 Histology
 Regional lymph node involvement
 The presence of metastasis

 For most solid tumors (e.g., breast, lung, kidney), cancer is broadly
classified (using roman numerals I-IV) into 4 stages
 Common Cancer Terms
Angiogenesis Development of new blood vessels to supply oxygen and
nutrients to cells

Apoptosis Programmed cell death

Cell cycle Phases of cell activity divided into G, S, and M (growth,

DNA synthesis, and mitosis, respectively)

Oncogene Encodes a protein that, when mutated, promotes

uncontrolled cell growth

Tumor Encodes a protein involved in protecting cells from

suppressor gene unregulated growth
Radiation
 Cancer can be detected and monitored using biologic tumor
markers.

 Tumor markers are produced either directly by the tumor or as an

effect of the tumor on healthy tissue (host).

 Tumor markers encompass an array of diverse molecules such as:

 Serum proteins
 Oncofetal antigens
 Hormones
 Metabolites
 Receptors
 Enzymes
 Applications of Tumor Marker
Detection
 Ideally, a tumor marker would be:
 tumor specific
 absent in healthy individuals
 readily detectable in body fluids.
 Unfortunately, all of the presently available tumor markers do not fit this
ideal model.
 However, a host of tumor markers have been identified that have a high
enough specificity & sensitivity to be used in:
 Screening populations at risk
 Diagnosis
 Prognosis
 Detection of recurrence
 Monitoring response to treatment.
 A tumor marker should have be present in or
produced by tumor itself
 A tumor marker should not be present in healthy
tissues
 Plasma level of a tumor marker should be at a
minimum level in healthy subjects and in benign
conditions
 A tumor marker should be specific for a tissue, it
should have different immunological properties when
it is synthesized in other tissues
 Plasma level of the tumor marker should be in
proportion to both size and activity of the tumor
 Half life of a tumor should not be very long
 A tumor marker should be present in plasma at a
detectable level, although tumor size is very small
 With possible exception of Prostate-Specific Antigen (PSA), no
tumor marker identified to date can be used to adequately screen
asymptomatic populations
 because most of the clinically used tumor markers are found in normal cells
and benign conditions in addition to cancer cells.

 Screening asymptomatic populations would therefore result in

detection of false-positives-(patients without disease with
detectable tumor marker), leading to undue alarm and cost to
patients.

 Presently, only a few tumor markers are used in populations with

high incidence or other carefully defined populations.
 Tumor marker concentration generally increases with tumor
progression, reaching their highest levels when tumors metastasize.
 Therefore, serum tumor marker levels at diagnosis can reflect the
aggressiveness of a tumor and help predict the outcome for patients.
 High serum tumor markers at diagnosis might indicate the presence
of malignancy and possible metastasis associated with a poorer
prognosis.
 In other instances, the mere presence or absence of a particular
marker may be valuable. Such is the case with some of the receptors
used to base chemotherapeutic treatment in breast cancer.
 Monitoring Effectiveness of Therapy
and Disease Recurrence
 One of the most useful applications of tumor markers is
monitoring therapy efficacy and detecting disease recurrence.

 After surgical resection, radiation, or drug therapy of cancer

(chemotherapy), tumor markers are routinely followed serially.

 In patients with elevated tumor markers at diagnosis, effective

therapy results in a dramatic decrease or disappearance of the
tumor marker.

 If the initial treatment is effective, the appearance of circulating

tumor markers can then be used as a highly sensitive marker of
recurrence.